MitoChip and MiSeq analysis

97 subjects were run through the Illumina MitoChip v2. Calls were processed using ReseqChip to obtain consensus sequences. These were processed through Mitomaster to obtain variants and Haplogroup calls (via Haplogrep).

96 subjects were sequenced on an Illumina MiSeq and aligned by CAG using bwa-mem to the g1k_v37 reference. Samtools/bcftools was used to create a consensus sequence for reads mapping to MT. These sequences were also processed through Mitomaster.

7 subjects were run on both platforms.

Population structure

Initial findings

Concordance of sequence and microarray data

Sequence and microarray microhaplogroups were identical between the 7 samples run on both platforms

Duplicate microarray samples were removed for the remainder for the analysis.

Regno cnt samples sources mhaps
821630 2 821630, Mito_AML1031_PT1_F09_821630 seq, chip U5a1a1d, U5a1a1d
822655 2 822655, Mito_AML1031_PT1_B02_822655 seq, chip C, C
823157 2 823157, Mito_AML1031_PT1_H09_823157 seq, chip K1a1b1a, K1a1b1a
825090 2 825090, Mito_AML1031_PT1_C10_825090 seq, chip H1, H1
828528 2 828528, Mito_AML1031_PT1_E03_828528 seq, chip H5, H5
829368 2 829368, Mito_AML1031_PT1_E07_829368 seq, chip C, C
830330 2 830330, Mito_AML1031_PT1_C11_830330 seq, chip H3a1, H3a1

Loci

A total of 953 loci witnessed variants in at least one subject.

A word of caution

rCRS is a somewhat arbitrary reference with microhaplogroup H2a2a1. Variants from the rCRS do not imply deleteriousness, and in many cases reference alleles are risk factors for disease or other non-optimal outcomes. It is just as important to weight “protective variants” equally.

Variants by genbank frequency

Mitomaster computes frequency of each variant in its corpus of 30,589 GenBank sequences.

Variants by haplogroup frequency

Mitomaster also computes frequency within minor haplogroups. Frequencies near 100% are likely haplogroup-defining variants

625 of the variants are very rare (<1%) could be Mitochip artefacts, especially if they appear in more than one subject. Others are more common than not, and reflect the oddity of rCRS as a reference.

The breakdown of macro haplogroups

Why are there so many Asians when that is not a self-reporting group? Here is the breakdown of Asian haplogroups:

macrohaplogroup count
A 13
B 8
C 9
D 5
M 3
N 1

What is the concordance with SVM PCA-component classified by Hapmap populations

These calls were made using the SVM’s trained on HapMap and the following breakdown:

EUR = CEU + TSI
AFR = ASW + LWK + MKK + YRI
MEX = MXL

See https://github.research.chop.edu/vujkovicm/aplenc_gwas/blob/master/R/pop_strat.R for the code.

The prevalance of A haplogroups associated with Amerindian populations in Mexico is historically consistent. See http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3051415/

Autosomal population background

Classification

Three principal components from population-defining SNPs were provided as courtesy by CAG.

The first two PCs against self reported ethnicity:

Left ventricular systolic dysfunction

Distribution

Cannot justify using parametric tests.

Macrohaplogroup analysis

macrohaplogroup cnt mean_lvsd
N 1 0.0000000
HV 5 0.6000000
K 13 0.7307692
L0 4 0.7500000
A 13 0.7692308
J 15 0.9000000
L1 4 1.0000000
B 8 1.1250000
T 16 1.1875000
H 56 1.2410714
I 4 1.2500000
D 5 1.4000000
U 16 1.4062500
W 1 1.5000000
C 9 1.6666667
L3 5 1.9000000
L2 1 3.0000000
M 3 3.0000000
R 1 3.0000000
X 2 3.0000000
V 4 NA

Linear model

## 
## Call:
## lm(formula = lvsd ~ macrohaplogroup, data = cpdf)
## 
## Residuals:
##     Min      1Q  Median      3Q     Max 
## -1.6667 -0.9000 -0.1875  0.7589  2.8125 
## 
## Coefficients:
##                   Estimate Std. Error t value Pr(>|t|)  
## (Intercept)        0.75000    0.56969   1.317   0.1898  
## macrohaplogroupL1  0.25000    0.80566   0.310   0.7567  
## macrohaplogroupL2  2.25000    1.27386   1.766   0.0792 .
## macrohaplogroupL3  1.15000    0.76431   1.505   0.1343  
## macrohaplogroupA   0.01923    0.65146   0.030   0.9765  
## macrohaplogroupB   0.37500    0.69772   0.537   0.5917  
## macrohaplogroupC   0.91667    0.68468   1.339   0.1825  
## macrohaplogroupD   0.65000    0.76431   0.850   0.3963  
## macrohaplogroupM   2.25000    0.87021   2.586   0.0106 *
## macrohaplogroupN  -0.75000    1.27386  -0.589   0.5568  
## macrohaplogroupHV -0.15000    0.76431  -0.196   0.8447  
## macrohaplogroupH   0.49107    0.58968   0.833   0.4062  
## macrohaplogroupI   0.50000    0.80566   0.621   0.5357  
## macrohaplogroupJ   0.15000    0.64116   0.234   0.8153  
## macrohaplogroupK  -0.01923    0.65146  -0.030   0.9765  
## macrohaplogroupR   2.25000    1.27386   1.766   0.0792 .
## macrohaplogroupT   0.43750    0.63693   0.687   0.4931  
## macrohaplogroupU   0.65625    0.63693   1.030   0.3044  
## macrohaplogroupV   0.41667    0.87021   0.479   0.6327  
## macrohaplogroupW   0.75000    1.27386   0.589   0.5568  
## macrohaplogroupX   2.25000    0.98672   2.280   0.0239 *
## ---
## Signif. codes:  0 '***' 0.001 '**' 0.01 '*' 0.05 '.' 0.1 ' ' 1
## 
## Residual standard error: 1.139 on 164 degrees of freedom
##   (1 observation deleted due to missingness)
## Multiple R-squared:  0.1548, Adjusted R-squared:  0.05169 
## F-statistic: 1.502 on 20 and 164 DF,  p-value: 0.08673

Do the PCA’s based on the microarrays help?

## 
## Call:
## lm(formula = lvsd ~ macrohaplogroup + pca1 + pca2 + pca3, data = cpdf)
## 
## Residuals:
##     Min      1Q  Median      3Q     Max 
## -1.6451 -0.8854 -0.1832  0.7770  2.7870 
## 
## Coefficients:
##                    Estimate Std. Error t value Pr(>|t|)  
## (Intercept)         0.58820    0.64384   0.914   0.3623  
## macrohaplogroupL1   0.18828    0.93498   0.201   0.8407  
## macrohaplogroupL2   2.16806    1.37375   1.578   0.1165  
## macrohaplogroupL3   1.07574    0.92999   1.157   0.2491  
## macrohaplogroupA    0.06747    0.70701   0.095   0.9241  
## macrohaplogroupB    0.23737    0.74730   0.318   0.7512  
## macrohaplogroupC    0.87464    0.75315   1.161   0.2472  
## macrohaplogroupD    0.50636    0.87655   0.578   0.5643  
## macrohaplogroupM    2.09012    0.94927   2.202   0.0291 *
## macrohaplogroupN   -0.51965    1.34086  -0.388   0.6989  
## macrohaplogroupHV   0.06500    0.85661   0.076   0.9396  
## macrohaplogroupH    0.69502    0.69466   1.001   0.3186  
## macrohaplogroupI    0.72554    0.90056   0.806   0.4216  
## macrohaplogroupJ    0.35143    0.74399   0.472   0.6373  
## macrohaplogroupK    0.19255    0.75819   0.254   0.7998  
## macrohaplogroupR    2.30424    1.32223   1.743   0.0833 .
## macrohaplogroupT    0.65549    0.74684   0.878   0.3814  
## macrohaplogroupU    0.85483    0.73829   1.158   0.2486  
## macrohaplogroupV    0.58175    0.91903   0.633   0.5276  
## macrohaplogroupW    0.96474    1.33748   0.721   0.4718  
## macrohaplogroupX    2.47013    1.06426   2.321   0.0215 *
## pca1              -15.04692   38.90261  -0.387   0.6994  
## pca2               15.18466   17.28941   0.878   0.3811  
## pca3               -2.44772   12.08871  -0.202   0.8398  
## ---
## Signif. codes:  0 '***' 0.001 '**' 0.01 '*' 0.05 '.' 0.1 ' ' 1
## 
## Residual standard error: 1.147 on 161 degrees of freedom
##   (1 observation deleted due to missingness)
## Multiple R-squared:  0.1597, Adjusted R-squared:  0.03969 
## F-statistic: 1.331 on 23 and 161 DF,  p-value: 0.1553

Nope.

All-by-all haplogroups kruskal-wallis

## 
##  Kruskal-Wallis rank sum test
## 
## data:  lvsd by macrohaplogroup
## Kruskal-Wallis chi-squared = 26.875, df = 20, p-value = 0.1388

Due to high variance, no macro haplogroup is significantly different

Haplogroup (letter-number-letter) analysis

haplogroup mean_lvsd
A2d 0.0000000
A2k 0.0000000
B2h 0.0000000
D1 0.0000000
H14b 0.0000000
H1g 0.0000000
H2 0.0000000
H27a 0.0000000
H31 0.0000000
H3v 0.0000000
H3y 0.0000000
H5b 0.0000000
H7a 0.0000000
H82 0.0000000
HV5 0.0000000
HV6 0.0000000
I1 0.0000000
J2b 0.0000000
K1 0.0000000
K1a 0.0000000
K2a 0.0000000
N1b 0.0000000
T2d 0.0000000
T2f 0.0000000
U4b 0.0000000
A2 0.2500000
L1c 0.3333333
T2b 0.4166667
H1e 0.5000000
L0a 0.7500000
J1c 0.8500000
A2o 1.0000000
A2u 1.0000000
B2a 1.0000000
B4c 1.0000000
C1b 1.0000000
D1d 1.0000000
D5b 1.0000000
H47 1.0000000
H4a 1.0000000
HV 1.0000000
I2d 1.0000000
I4a 1.0000000
U2e 1.0000000
H1b 1.1000000
H5a 1.1000000
K1c 1.1666667
H1a 1.1875000
U5a 1.2142857
J1b 1.2500000
L3d 1.2500000
B2 1.3333333
H16b 1.3333333
A2a 1.4000000
H1y 1.5000000
H2a 1.5000000
U6a 1.5000000
W 1.5000000
B4b 2.0000000
D4b 2.0000000
H1 2.0000000
H11a 2.0000000
H6a 2.0000000
K1b 2.0000000
K2b 2.0000000
L3b 2.0000000
M71a 2.0000000
U3a 2.0000000
U5b 2.0000000
T1a 2.0833333
C 2.5000000
C1c 2.5000000
L3e 2.5000000
D4j 3.0000000
H15a 3.0000000
H24a 3.0000000
H3 3.0000000
H5 3.0000000
I2 3.0000000
L1b 3.0000000
L2a 3.0000000
M7b 3.0000000
R5a 3.0000000
X2c 3.0000000
X2e 3.0000000
H3a 4.0000000
M5a 4.0000000
T1 4.0000000
V NA

Linear model

## 
## Call:
## lm(formula = lvsd ~ haplogroup, data = cpdf)
## 
## Residuals:
##     Min      1Q  Median      3Q     Max 
## -2.0000 -0.3333  0.0000  0.3333  2.1500 
## 
## Coefficients:
##                Estimate Std. Error t value Pr(>|t|)   
## (Intercept)     0.25000    0.51069   0.490  0.62558   
## haplogroupA2a   1.15000    0.68516   1.678  0.09651 . 
## haplogroupA2d  -0.25000    1.14193  -0.219  0.82717   
## haplogroupA2k  -0.25000    1.14193  -0.219  0.82717   
## haplogroupA2o   0.75000    1.14193   0.657  0.51289   
## haplogroupA2u   0.75000    1.14193   0.657  0.51289   
## haplogroupB2    1.08333    0.78009   1.389  0.16813   
## haplogroupB2a   0.75000    0.88453   0.848  0.39860   
## haplogroupB2h  -0.25000    1.14193  -0.219  0.82717   
## haplogroupB4b   1.75000    1.14193   1.532  0.12869   
## haplogroupB4c   0.75000    1.14193   0.657  0.51289   
## haplogroupC     2.25000    0.88453   2.544  0.01256 * 
## haplogroupC1b   0.75000    0.68516   1.095  0.27641   
## haplogroupC1c   2.25000    0.88453   2.544  0.01256 * 
## haplogroupD1   -0.25000    1.14193  -0.219  0.82717   
## haplogroupD1d   0.75000    1.14193   0.657  0.51289   
## haplogroupD4b   1.75000    1.14193   1.532  0.12869   
## haplogroupD4j   2.75000    1.14193   2.408  0.01794 * 
## haplogroupD5b   0.75000    1.14193   0.657  0.51289   
## haplogroupH1    1.75000    0.72222   2.423  0.01726 * 
## haplogroupH11a  1.75000    0.72222   2.423  0.01726 * 
## haplogroupH14b -0.25000    1.14193  -0.219  0.82717   
## haplogroupH15a  2.75000    1.14193   2.408  0.01794 * 
## haplogroupH16b  1.08333    0.78009   1.389  0.16813   
## haplogroupH1a   0.93750    0.62546   1.499  0.13718   
## haplogroupH1b   0.85000    0.68516   1.241  0.21778   
## haplogroupH1e   0.25000    0.88453   0.283  0.77807   
## haplogroupH1g  -0.25000    0.88453  -0.283  0.77807   
## haplogroupH1y   1.25000    1.14193   1.095  0.27641   
## haplogroupH2   -0.25000    1.14193  -0.219  0.82717   
## haplogroupH24a  2.75000    1.14193   2.408  0.01794 * 
## haplogroupH27a -0.25000    1.14193  -0.219  0.82717   
## haplogroupH2a   1.25000    0.78009   1.602  0.11236   
## haplogroupH3    2.75000    1.14193   2.408  0.01794 * 
## haplogroupH31  -0.25000    0.88453  -0.283  0.77807   
## haplogroupH3a   3.75000    1.14193   3.284  0.00143 **
## haplogroupH3v  -0.25000    1.14193  -0.219  0.82717   
## haplogroupH3y  -0.25000    1.14193  -0.219  0.82717   
## haplogroupH47   0.75000    1.14193   0.657  0.51289   
## haplogroupH4a   0.75000    1.14193   0.657  0.51289   
## haplogroupH5    2.75000    1.14193   2.408  0.01794 * 
## haplogroupH5a   0.85000    0.68516   1.241  0.21778   
## haplogroupH5b  -0.25000    1.14193  -0.219  0.82717   
## haplogroupH6a   1.75000    0.88453   1.978  0.05074 . 
## haplogroupH7a  -0.25000    1.14193  -0.219  0.82717   
## haplogroupH82  -0.25000    1.14193  -0.219  0.82717   
## haplogroupHV    0.75000    0.78009   0.961  0.33875   
## haplogroupHV5  -0.25000    1.14193  -0.219  0.82717   
## haplogroupHV6  -0.25000    1.14193  -0.219  0.82717   
## haplogroupI1   -0.25000    1.14193  -0.219  0.82717   
## haplogroupI2    2.75000    1.14193   2.408  0.01794 * 
## haplogroupI2d   0.75000    1.14193   0.657  0.51289   
## haplogroupI4a   0.75000    1.14193   0.657  0.51289   
## haplogroupJ1b   1.00000    0.72222   1.385  0.16938   
## haplogroupJ1c   0.60000    0.60425   0.993  0.32322   
## haplogroupJ2b  -0.25000    1.14193  -0.219  0.82717   
## haplogroupK1   -0.25000    0.88453  -0.283  0.77807   
## haplogroupK1a  -0.25000    0.78009  -0.320  0.74930   
## haplogroupK1b   1.75000    1.14193   1.532  0.12869   
## haplogroupK1c   0.91667    0.78009   1.175  0.24287   
## haplogroupK2a  -0.25000    0.88453  -0.283  0.77807   
## haplogroupK2b   1.75000    0.88453   1.978  0.05074 . 
## haplogroupL0a   0.50000    0.72222   0.692  0.49041   
## haplogroupL1b   2.75000    1.14193   2.408  0.01794 * 
## haplogroupL1c   0.08333    0.78009   0.107  0.91515   
## haplogroupL2a   2.75000    1.14193   2.408  0.01794 * 
## haplogroupL3b   1.75000    1.14193   1.532  0.12869   
## haplogroupL3d   1.00000    0.88453   1.131  0.26107   
## haplogroupL3e   2.25000    0.88453   2.544  0.01256 * 
## haplogroupM5a   3.75000    1.14193   3.284  0.00143 **
## haplogroupM71a  1.75000    1.14193   1.532  0.12869   
## haplogroupM7b   2.75000    1.14193   2.408  0.01794 * 
## haplogroupN1b  -0.25000    1.14193  -0.219  0.82717   
## haplogroupR5a   2.75000    1.14193   2.408  0.01794 * 
## haplogroupT1    3.75000    1.14193   3.284  0.00143 **
## haplogroupT1a   1.83333    0.65929   2.781  0.00653 **
## haplogroupT2b   0.16667    0.65929   0.253  0.80097   
## haplogroupT2d  -0.25000    1.14193  -0.219  0.82717   
## haplogroupT2f  -0.25000    0.88453  -0.283  0.77807   
## haplogroupU2e   0.75000    1.14193   0.657  0.51289   
## haplogroupU3a   1.75000    1.14193   1.532  0.12869   
## haplogroupU4b  -0.25000    1.14193  -0.219  0.82717   
## haplogroupU5a   0.96429    0.64018   1.506  0.13528   
## haplogroupU5b   1.75000    0.72222   2.423  0.01726 * 
## haplogroupU6a   1.25000    0.88453   1.413  0.16084   
## haplogroupV     0.91667    0.78009   1.175  0.24287   
## haplogroupW     1.25000    1.14193   1.095  0.27641   
## haplogroupX2c   2.75000    1.14193   2.408  0.01794 * 
## haplogroupX2e   2.75000    1.14193   2.408  0.01794 * 
## ---
## Signif. codes:  0 '***' 0.001 '**' 0.01 '*' 0.05 '.' 0.1 ' ' 1
## 
## Residual standard error: 1.021 on 96 degrees of freedom
##   (1 observation deleted due to missingness)
## Multiple R-squared:  0.6024, Adjusted R-squared:  0.2379 
## F-statistic: 1.653 on 88 and 96 DF,  p-value: 0.008189

All-by-all haplogroups kruskal-wallis

## 
##  Kruskal-Wallis rank sum test
## 
## data:  lvsd by haplogroup
## Kruskal-Wallis chi-squared = 106.96, df = 88, p-value = 0.0827

LVSD vs superpopulation and autosomal population

Autosomal background on x-facet, mitochondrial superpopulation on the y-facet. LVSD on the y-axis, SNP-chip PCA component 1 on the x-axis.

Mitochondrial superpopulation on the x-facet, LVSD on the y-facet. PCA’s on the axes.

Micro haplogroup

Individual variants on LVSD

Potentially deleterious mutations in cohort

Subjects with potentially deleterious mutations with Genbank frequency <= 1% are below.

patientphenotype cnt allele gb_perc subjects meanlvsd
ADPD / Possibly LVNC-cardiomyopathy associated 1 A3397G 0.3 833333 0.000000
Adult-Onset Dystonia 1 A3796G 0.54 835021 1.000000
BD-associated 1 C114T 0.45 823157 0.000000
Cardiomyopathy 1 G3337A 0.16 833306 1.000000
CPEO 1 T12311C 0.11 813584 1.500000
Cyclic Vomiting Syndrome with Migraine 1 C16176T 0.71 833333 0.000000
DEAF 1 T1005C 0.38 824932 0.000000
DEAF enhancer 1 T5655C 0.86 834220 3.000000
DEAF, possibly LVNC-associated 3 T961C 0.99 825058, 826309, 845419 1.333333
Hypertensive end-stage renal disease 1 A10086G 0.55 838492 2.000000
LHON 7 A8836G, C3497T, G15812A, T14325C, G3736A, A4381G 0.28, 0.36, 0.66, 0.1, 0.18, 0.01 819620, 824821, 828405, 843680, 845137… 1.142857
LHON / LDYT / DEAF / hypertension helper mut. 1 G11696A 0.51 817016 3.000000
LHON / SNHL / DEAF 1 G7444A 0.37 816146 0.000000
LHON modulator 1 A15951G 0.96 841810 2.000000
LHON-like, LHON, MELAS 1 A13528G 0.1 830998 0.000000
LHON; PD 2 T11253C 0.62 827360, 833788 2.000000
MELAS / DEAF enhancer / hypertension / LVNC 1 T3308C 0.95 834220 3.000000
Poss. hypertension factor 1 G3277A 0.06 823334 2.000000
possible HCM susceptibility 4 T12477C, G13135A 0.66, 0.87 817189, 823148, 823884, 830097 2.000000
Possibly DEAF-associated 4 T961G 0.38 825415, 825906, 829530, 838893 2.000000
Possibly LVNC-associated 3 T921C, A2755G 0.69, 0.57 813584, 826552, 833306 1.166667
Prostate Cancer 4 A7158G, T7080C, C5911T 0.07, 0.1, 0.46 813584, 814994, 839722, 845419 1.125000
Prostate Cancer / enriched in POAG cohort 1 G6480A 0.38 825205 1.000000
Prostate Cancer / hypertension 2 G5913A 0.75 819620, 839771 1.000000
Varied familial presentation / spastic paraparesis 1 G4284A 0.01 845137 1.000000
DEAF helper mut. 1 T10454C 0.37 821863 0.000000
DMDF+HCM / GDM / possibly LVNC cardiomyopathy-associated 1 T3398C 0.36 828754 0.000000
Myopathy 1 T5567C 0.09 823919 0.000000
Possible LHON factor 2 T12811C, A13637G 0.91, 0.9 819758, 820935 3.000000
Susceptibility to bullous pemphigoid 1 G8519A 0.26 828793 1.000000
Therapy-Resistant Epilepsy 1 C6489A 0.21 826789 0.000000
Thyroid Cancer Cell Line 1 A12634G 0.28 826552 1.000000

High LVSD variants

The following variants are found in at least 2 high (>=2.0) LVSD subjects but never in very low (<1.0) subjects

tpos cnt gb_avg allele locus effect haps hap_percs subjects
225 2 0.77 G225A HVS2/OH/CSB1/ATT/D-Loop non-coding X2e, X2c 20.69, 95.71 822335, 843690
239 3 1.31 T239C HVS2/OH/TFX/ATT/D-Loop non-coding T1, H6a, H6a 0, 96.59, 96.59 823081, 827360, 833788
2387 2 0.24 T2387C 16S rRNA J1c, J1c 3.92, 3.92 822754, 841525
3915 2 1.30 G3915A ND1 syn:G=>G H6a, H6a 99.62, 99.62 827360, 833788
4164 2 1.04 A4164G ND1 syn:M=>M M7b, H5a 97.64, 0.32 819758, 843976
4727 2 0.80 A4727G ND2 syn:M=>M H6a, H6a 95.83, 95.83 827360, 833788
5198 2 0.28 A5198G ND2 syn:L=>L J1c, J1c 10.37, 10.37 822754, 841525
5773 2 1.10 G5773A C/OL tRNA L3b, C1c 100, 7.02 838492, 840544
6216 3 0.56 T6216C COI syn:L=>L U3a, C, B4b 0, 0, 68.57 826190, 829368, 829844
6253 2 1.11 T6253C COI non-syn:M=>T C1c, H15a 0, 100 828232, 841130
6371 2 1.06 C6371T COI syn:S=>S X2e, X2c 100, 98.57 822335, 843690
6620 2 1.08 T6620C COI syn:G=>G K1b, J1b 0, 0 839771, 843613
7768 2 1.85 A7768G COII syn:M=>M U5b, U5b 99.49, 99.49 820935, 832692
8718 2 0.13 A8718G ATPase6 syn:K=>K M71a, X2e 100, 0 817517, 822335
9380 2 1.10 G9380A COIII syn:W=>W H6a, H6a 98.86, 98.86 827360, 833788
9899 5 1.06 T9899C COIII syn:H=>H T1a, T1, T1a, T1a, T1a 69.25, 14.29, 69.25, 69.25, 69.25 822682, 823081, 825611, 830311, 836578
10192 2 0.19 C10192T ND3 non-syn:S=>F J1c, J1c 3.8, 3.8 822754, 841525
10819 2 2.10 A10819G ND4 syn:K=>K L3e, L3e 99.03, 99.03 823334, 835638
11002 2 0.95 A11002G ND4 syn:Q=>Q L3b, X2c 81.41, 0 838492, 843690
11253 2 0.62 T11253C ND4 non-syn:I=>T H6a, H6a 52.65, 52.65 827360, 833788
12633 5 1.21 C12633A ND5 syn:S=>S T1a, T1, T1a, T1a, T1a 99.72, 100, 99.72, 99.72, 99.72 822682, 823081, 825611, 830311, 836578
13635 2 0.26 T13635C ND5 syn:G=>G C1b, R5a 5.88, 78.72 818376, 837392
13879 2 0.78 T13879C ND5 non-syn:S=>P J1b, J1b 63.98, 63.98 823389, 843613
13966 2 1.40 A13966G ND5 non-syn:T=>A X2e, X2c 100, 100 822335, 843690
14040 2 0.52 G14040A ND5 syn:Q=>Q R5a, L3b 74.47, 0 837392, 838492
14470 2 1.66 T14470C ND6 syn:G=>G X2e, X2c 100, 100 822335, 843690
15758 2 0.88 A15758G Cytb non-syn:I=>V I2, H1a 100, 1.93 826990, 843449
15784 2 3.29 T15784C Cytb syn:P=>P U5b, L2a 0, 89.68 832692, 844845
15930 3 2.55 G15930A T/ATT tRNA C, C1c, C1c 17.22, 100, 100 822655, 828232, 840544
16051 2 2.59 A16051G ATT/D-Loop/HVS1 non-coding K2b, C 1.47, 19.87 823148, 829368
16186 2 1.24 C16186T ATT/D-Loop/HVS1/7S DNA non-coding T1a, T1a 95.57, 95.57 830311, 836578
16192 4 4.27 C16192T ATT/D-Loop/HVS1/7S DNA non-coding U5a, H6a, A2a, J1b 57.1, 1.14, 37.89, 5.93 825058, 827360, 833572, 843613
16218 2 0.62 C16218T ATT/D-Loop/HVS1/7S DNA non-coding HV, L0a 0, 0.27 816255, 845419
16239 2 0.56 C16239T, C16239G ATT/D-Loop/HVS1/7S DNA non-coding H1, H3a 7.34, 15.7 825090, 830330
16256 2 3.60 C16256T ATT/D-Loop/HVS1/7S DNA non-coding U5a, H3a 94.01, 9.09 825058, 830330
16270 6 5.28 C16270T ATT/D-Loop/HVS1/7S DNA non-coding H1b, U5b, K2b, U5a, U5b, L1b 7.01, 85.14, 45.59, 93.04, 85.14, 90.64 816856, 820935, 823148, 825058, 832692, 834220
16482 2 0.77 A16482G ATT/D-Loop/7S DNA non-coding H6a, H6a 79.55, 79.55 827360, 833788

The following variants are found in at least 2 very low (<1.0) LVSD subjects but never in high (>=2.0) subjects

tpos cnt gb_avg allele locus effect haps hap_percs subjects
64 5 2.9600000 C64T HVS2/ATT/D-Loop/7S DNA non-coding A2, A2d, L0a, A2a, A2k 75.42, 58.33, 54.62, 42.86, 80 823919, 824388, 825390, 827091, 837615
143 2 2.1900000 G143A HVS2/OH/ATT/D-Loop/7S DNA non-coding A2, C1b 4.47, 4.58 823919, 828014
151 2 3.1800000 C151T HVS2/OH/ATT/D-Loop/7S DNA non-coding L1c, L1c 72.59, 72.59 820786, 846683
228 2 2.7300000 G228A HVS2/OH/CSB1/ATT/D-Loop non-coding J1c, J1c 79.15, 79.15 817189, 821863
236 2 1.3800000 T236C HVS2/OH/TFX/ATT/D-Loop non-coding L0a, L0a 93.48, 93.48 825390, 839722
249 2 0.0850000 A249T, A249G HVS2/OH/TFX/ATT/D-Loop non-coding C1b, H5b 0, 1.85 828014, 841150
316 2 1.6300000 G316A HVS2/OH/ATT/D-Loop non-coding L1c, L1c 95.18, 95.18 820786, 846683
497 2 2.5800000 C497T ATT/D-Loop non-coding K1a, K1a 96.93, 96.93 823157, 840957
930 4 2.0400000 G930A 12S rRNA T2b, T2b, T2b, T2b 99.24, 99.24, 99.24, 99.24 821395, 821837, 828754, 832668
1048 2 3.6900000 C1048T 12S rRNA L0a, L0a 100, 100 825390, 839722
1692 2 0.2700000 A1692T, A1692G 16S rRNA U6a, U4b 21.1, 0 817443, 830998
2245 2 1.1100000 A2245G 16S rRNA L0a, L0a 89.67, 89.67 825390, 839722
3516 2 3.2700000 C3516A ND1 syn:L=>L L0a, L0a 99.73, 99.73 825390, 839722
4312 2 3.2800000 C4312T I tRNA L0a, L0a 99.73, 99.73 825390, 839722
4561 2 0.7800000 T4561C ND2 non-syn:V=>A K2a, K2a 100, 100 816468, 844801
4586 2 1.5800000 T4586C ND2 syn:A=>A L0a, L0a 100, 100 825390, 839722
5147 5 4.1200000 G5147A ND2 syn:T=>T T2b, T2b, L0a, T2b, T2b 99.62, 99.62, 50, 99.62, 99.62 821395, 821837, 825390, 828754, 832668
5426 2 1.0500000 T5426C ND2 syn:H=>H T2b, T2f 1.14, 94.83 821837, 826789
5442 2 4.4300000 T5442C ND2 non-syn:F=>L L0a, L0a 99.73, 99.73 825390, 839722
5471 3 1.0600000 G5471A ND2 syn:T=>T U6a, N1b, H5b 22.48, 98.86, 100 817443, 819620, 841150
5603 2 1.2900000 C5603T A tRNA L0a, L0a 97.83, 97.83 825390, 839722
5951 2 1.4600000 A5951G COI syn:G=>G L1c, L1c 99.34, 99.34 820786, 846683
6071 2 1.4700000 T6071C COI syn:V=>V L1c, L1c 99.56, 99.56 820786, 846683
6185 2 3.3600000 T6185C COI syn:F=>F L0a, L0a 100, 100 825390, 839722
6917 2 0.3600000 G6917A COI syn:V=>V L1c, L1c 18.42, 18.42 820786, 846683
7389 3 2.4200000 T7389C COI non-syn:Y=>H L1c, A2, L1c 99.78, 2.23, 99.78 820786, 825934, 846683
7930 2 0.1300000 A7930T COII syn:G=>G H31, H31 96.43, 96.43 836223, 838511
8251 3 6.4400000 G8251A COII syn:G=>G N1b, L1c, I1 96.59, 17.32, 100 819620, 820786, 826457
8428 2 1.1600000 C8428T ATPase8 syn:F=>F L0a, L0a 100, 100 825390, 839722
8460 2 0.6400000 A8460G ATPase8 non-syn:N=>S L0a, A2k 48.91, 60 825390, 837615
8566 2 1.2300000 A8566G ATPase8/ATPase6 syn:Q=>Q L0a, L0a 100, 100 825390, 839722
8602 2 0.1600000 T8602C ATPase6 non-syn:F=>L H1g, H1g 97.3, 97.3 826167, 829029
9042 2 3.2900000 C9042T ATPase6 syn:H=>H L0a, L0a 100, 100 825390, 839722
9055 3 4.9300000 G9055A ATPase6 non-syn:A=>T K1a, K1a, K2a 99.17, 99.17, 100 823157, 840957, 844801
9072 2 1.4300000 A9072G ATPase6 syn:S=>S L1c, L1c 99.56, 99.56 820786, 846683
9347 2 3.2500000 A9347G COIII syn:L=>L L0a, L0a 100, 100 825390, 839722
9716 2 1.0300000 T9716C COIII syn:G=>G K2a, K2a 100, 100 816468, 844801
9755 3 3.1300000 G9755A COIII syn:E=>E J1c, L0a, L0a 1.73, 100, 100 821908, 825390, 839722
9818 2 1.5700000 C9818T COIII syn:H=>H L0a, L0a 100, 100 825390, 839722
9966 2 0.6900000 G9966A COIII non-syn:V=>I I1, L1c 96.67, 8.77 826457, 846683
10238 2 6.2600000 T10238C ND3 syn:I=>I N1b, I1 98.86, 100 819620, 826457
10586 2 1.8700000 G10586A ND4L syn:S=>S L1c, L1c 99.56, 99.56 820786, 846683
10664 2 3.2800000 C10664T ND4L syn:V=>V L0a, L0a 100, 100 825390, 839722
10771 2 0.1400000 A10771G ND4 syn:L=>L H31, H31 92.86, 92.86 836223, 838511
10915 2 3.9900000 T10915C ND4 syn:C=>C L0a, L0a 99.18, 99.18 825390, 839722
11176 2 1.4500000 G11176A ND4 syn:Q=>Q L0a, L0a 100, 100 825390, 839722
11302 2 0.2700000 C11302T ND4 syn:L=>L L1c, L1c 18.42, 18.42 820786, 846683
11314 2 0.2000000 A11314G ND4 syn:E=>E L1c, A2d 0, 45.83 820786, 824388
11641 2 1.2900000 A11641G ND4 syn:M=>M L0a, L0a 100, 100 825390, 839722
11812 7 3.3000000 A11812G ND4 syn:L=>L T2f, T2b, T2b, T2d, T2f, T2b, T2b 100, 99.43, 99.43, 100, 100, 99.43, 99.43 818356, 821395, 821837, 821949, 826789, 828754, 832668
12720 2 3.0500000 A12720G ND5 syn:M=>M L0a, L0a 99.46, 99.46 825390, 839722
12810 2 2.2900000 A12810G ND5 syn:W=>W L1c, L1c 99.56, 99.56 820786, 846683
13276 2 3.2400000 A13276G ND5 non-syn:M=>V L0a, L0a 99.18, 99.18 825390, 839722
13485 2 1.4200000 A13485G ND5 syn:M=>M L1c, L1c 98.68, 98.68 820786, 846683
13789 2 2.2700000 T13789C ND5 non-syn:Y=>H L1c, L1c 99.78, 99.78 820786, 846683
13934 5 1.1900000 C13934T ND5 non-syn:T=>M J1c, D1, J1c, J1c, J1c 19.93, 0.94, 19.93, 19.93, 19.93 817189, 817866, 821640, 821863, 821908
14000 2 1.4600000 T14000A ND5 non-syn:L=>Q L1c, L1c 99.78, 99.78 820786, 846683
14106 2 0.0800000 T14106C ND5 syn:S=>S A2, L0a 0.56, 4.89 823919, 839722
14178 3 2.7700000 T14178C ND6 non-syn:I=>V L1c, H27a, L1c 99.78, 0, 99.78 820786, 831554, 846683
14233 7 3.6600000 A14233G ND6 syn:D=>D T2f, T2b, T2b, T2d, T2f, T2b, T2b 98.28, 99.24, 99.24, 100, 98.28, 99.24, 99.24 818356, 821395, 821837, 821949, 826789, 828754, 832668
14305 2 0.5600000 G14305A ND6 syn:S=>S K2a, K2a 23.24, 23.24 816468, 844801
14308 2 1.7400000 T14308C ND6 syn:G=>G L0a, L0a 97.28, 97.28 825390, 839722
14560 2 2.7900000 G14560A ND6 syn:V=>V L1c, L1c 99.34, 99.34 820786, 846683
14911 2 1.4300000 C14911T Cytb syn:Y=>Y L1c, L1c 98.68, 98.68 820786, 846683
15136 2 1.2200000 C15136T Cytb syn:G=>G L0a, L0a 100, 100 825390, 839722
15226 2 0.3300000 A15226G Cytb syn:L=>L L1c, L1c 17.98, 17.98 820786, 846683
15431 2 1.5900000 G15431A Cytb non-syn:A=>T L0a, L0a 99.73, 99.73 825390, 839722
15905 2 0.3900000 T15905C T tRNA L1c, L1c 17.98, 17.98 820786, 846683
15924 4 4.0200000 A15924G T tRNA N1b, K1a, I1, A2k 1.14, 14.64, 93.33, 80 819620, 823157, 826457, 837615
15978 2 0.3000000 C15978T P/ATT tRNA L1c, L1c 18.42, 18.42 820786, 846683
16176 2 0.4600000 C16176G, C16176T ATT/D-Loop/HVS1/7S DNA non-coding N1b, H82 73.86, 0 819620, 833333
16179 2 0.7200000 C16179T ATT/D-Loop/HVS1/7S DNA non-coding K1c, B2 0, 0.67 815368, 816146
16188 2 0.9800000 C16188G ATT/D-Loop/HVS1/7S DNA non-coding L0a, L0a 82.88, 82.88 825390, 839722
16209 2 2.7200000 T16209C ATT/D-Loop/HVS1/7S DNA non-coding L1c, H1a 5.26, 15.09 820786, 833669
16215 2 0.2500000 A16215G ATT/D-Loop/HVS1/7S DNA non-coding H1e, L1c 0.51, 7.46 823637, 846683
16220 2 0.1950000 A16220C, A16220G ATT/D-Loop/HVS1/7S DNA non-coding H1b, H82 2.74, 100 826379, 833333
16222 2 0.8100000 C16222T ATT/D-Loop/HVS1/7S DNA non-coding J1b, J1b 73.73, 73.73 819501, 836933
16224 4 5.0000000 T16224C ATT/D-Loop/HVS1/7S DNA non-coding T2b, K1a, K1a, K2a 0.38, 95.4, 95.4, 95.14 821395, 823157, 840957, 844801
16230 2 3.1600000 A16230G ATT/D-Loop/HVS1/7S DNA non-coding L0a, L0a 94.02, 94.02 825390, 839722
16261 2 7.4700000 C16261T ATT/D-Loop/HVS1/7S DNA non-coding J1b, H7a 95.76, 83.33 836933, 841268
16316 3 0.2933333 A16316T, A16316G ATT/D-Loop/HVS1/7S DNA non-coding A2a, A2a, H27a 0, 0, 100 817954, 827091, 831554
16317 3 0.0000000 A16317C ATT/D-Loop/HVS1/7S DNA non-coding C1b, A2a, C1b 0, 0, 0 824932, 827091, 828014

mtGWAS

GLM using both haplogroup and non-haplogroup defining variants

p.value < 0.05 before correction for multiple testing

tpos hapsnp_p.val tnt qnt calc_locus gb_perc allele haps hap_percs subjects mean_lvsd
225 0.0238794 G A HVS2/OH/CSB1/ATT/D-Loop 0.77 G225A X2e 20.69 822335 3.000
239 0.0243111 T C HVS2/OH/TFX/ATT/D-Loop 1.31 T239C T1 0 823081 4.000
437 0.0411979 C T OH/PL/TFL/ATT/D-Loop 0.07 C437T A2a 1.86 823650 3.000
487 0.0411979 A G ATT/D-Loop 0.02 A487G A2a 2.48 823650 3.000
2387 0.0324802 T C 16S 0.24 T2387C J1c, J1c 3.92, 3.92 822754, 841525 2.500
3565 0.0411979 A G ND1 0.10 A3565G A2a 2.48 823650 3.000
5046 0.0423120 G A ND2 2.15 G5046A W 0 834209 1.500
5102 0.0140978 A G ND2 0.01 A5102G H11a 0 825906 4.000
5147 0.0203247 G A ND2 4.12 G5147A L0a, L0a 50, 50 825390, 845137 0.500
5198 0.0324802 A G ND2 0.28 A5198G J1c, J1c 10.37, 10.37 822754, 841525 2.500
5252 0.0140978 G A ND2 0.34 G5252A H11a 0 825906 4.000
5461 0.0377832 C T ND2 0.03 C5461T K2b 0 823148 3.000
5985 0.0103637 G A COI 0.11 G5985A T1 0 823081 4.000
6446 0.0423120 G A COI 0.69 G6446A L1b 2.25 834220 3.000
7307 0.0411979 A G COI 0.02 A7307G A2a 1.86 823650 3.000
9458 0.0423120 C T COIII 0.17 C9458T L1b 1.12 834220 3.000
9899 0.0002890 T C COIII 1.06 T9899C T1a, T1, T1a, T1a, T1a, T1a 69.25, 14.29, 69.25, 69.25, 69.25, 69.25 822682, 823081, 825121, 825611, 830311, 836578 2.500
10192 0.0324802 C T ND3 0.19 C10192T J1c, J1c 3.8, 3.8 822754, 841525 2.500
11812 0.0058209 A G ND4 3.30 A11812G C1b 1.96 846183 3.000
14587 0.0140978 A G ND6 0.53 A14587G H11a 28.8 825906 4.000
15236 0.0411979 A G Cytb 1.10 A15236G A2a 0 823650 3.000
15412 0.0411979 T C Cytb 0.11 T15412C A2a 0 823650 3.000
16092 0.0140978 T C ATT/D-Loop/HVS1 1.47 T16092C H11a 24 825906 4.000
16163 0.0032930 A G ATT/D-Loop/HVS1/7S DNA/TAS 1.40 A16163G L1c, T1 8.55, 57.14 820786, 823081 2.000
16239 0.0039954 C G ATT/D-Loop/HVS1/7S DNA 0.06 C16239G H3a 15.7 830330 4.000
16239 0.0039954 C T ATT/D-Loop/HVS1/7S DNA 1.06 C16239T H1 7.34 825090 3.000
16254 0.0140978 A G ATT/D-Loop/HVS1/7S DNA 0.13 A16254G H11a 0 825906 4.000
16270 0.0101111 C T ATT/D-Loop/HVS1/7S DNA 5.28 C16270T H1b, K2b, H1b, K2b 7.01, 45.59, 7.01, 45.59 816856, 823148, 827951, 830097 1.875
16293 0.0247849 A G ATT/D-Loop/HVS1/7S DNA 2.28 A16293G L0a, L0a 27.17, 27.17 839722, 845419 1.000
16317 0.0217274 A C ATT/D-Loop/HVS1/7S DNA 0.00 A16317C C1b, A2a, C1b 0, 0, 0 824932, 827091, 828014 0.000

GLM - non-haplogroup defining variants only

p.value < 0.05 before correction for multiple testing

tpos snponly_p.val qnt tnt calc_locus gb_perc allele haps hap_percs subjects mean_lvsd
151 0.0449163 T C HVS2/OH/ATT/D-Loop/7S DNA 3.18 C151T L1c, L1c 72.59, 72.59 820786, 846683 0.000
154 0.0339510 C T HVS2/OH/ATT/D-Loop/7S DNA 0.07 T154C M5a 0.85 823884 4.000
225 0.0220812 A G HVS2/OH/CSB1/ATT/D-Loop 0.77 G225A X2e 20.69 822335 3.000
239 0.0291555 C T HVS2/OH/TFX/ATT/D-Loop 1.31 T239C T1 0 823081 4.000
5102 0.0127407 G A ND2 0.01 A5102G H11a 0 825906 4.000
5147 0.0445695 A G ND2 4.12 G5147A L0a, L0a 50, 50 825390, 845137 0.500
5252 0.0127407 A G ND2 0.34 G5252A H11a 0 825906 4.000
5985 0.0139742 A G COI 0.11 G5985A T1 0 823081 4.000
6917 0.0449163 A G COI 0.36 G6917A L1c, L1c 18.42, 18.42 820786, 846683 0.000
9899 0.0031598 C T COIII 1.06 T9899C T1a, T1, T1a, T1a, T1a, T1a 69.25, 14.29, 69.25, 69.25, 69.25, 69.25 822682, 823081, 825121, 825611, 830311, 836578 2.500
11302 0.0449163 T C ND4 0.27 C11302T L1c, L1c 18.42, 18.42 820786, 846683 0.000
12681 0.0339510 C T ND5 0.20 T12681C M5a 1.69 823884 4.000
13105 0.0418467 G A ND5 7.77 A13105G D1d 40 823260 1.000
14587 0.0127407 G A ND6 0.53 A14587G H11a 28.8 825906 4.000
15226 0.0449163 G A Cytb 0.33 A15226G L1c, L1c 17.98, 17.98 820786, 846683 0.000
15301 0.0376168 A G Cytb 27.55 G15301A B4c 40.74 824821 1.000
15784 0.0416055 C T Cytb 3.29 T15784C U5b 0 832692 3.000
15978 0.0449163 T C P/ATT 0.30 C15978T L1c, L1c 18.42, 18.42 820786, 846683 0.000
16092 0.0127407 C T ATT/D-Loop/HVS1 1.47 T16092C H11a 24 825906 4.000
16163 0.0279064 G A ATT/D-Loop/HVS1/7S DNA/TAS 1.40 A16163G L1c, T1 8.55, 57.14 820786, 823081 2.000
16239 0.0033374 G C ATT/D-Loop/HVS1/7S DNA 0.06 C16239G H3a 15.7 830330 4.000
16239 0.0033374 T C ATT/D-Loop/HVS1/7S DNA 1.06 C16239T H1 7.34 825090 3.000
16254 0.0127407 G A ATT/D-Loop/HVS1/7S DNA 0.13 A16254G H11a 0 825906 4.000
16270 0.0188273 T C ATT/D-Loop/HVS1/7S DNA 5.28 C16270T H1b, K2b, H1b, K2b 7.01, 45.59, 7.01, 45.59 816856, 823148, 827951, 830097 1.875

GLMs

Haplogroups of interest

H

Enrichment

Are there any differences in variants between the 10 >=3’s and the 21 0’s?

Enriched in high LVSD (>1fc)

tpos tnt qnt calc_locus gb_perc hot cold enrichment allele
55 T C ATT/D-Loop/7S DNA 0.20 1 0 Inf T55C
57 T C HVS2/ATT/D-Loop/7S DNA 0.20 1 0 Inf T57C
73 A G HVS2/ATT/D-Loop/7S DNA 73.71 1 1 1.070389 A73G
189 A C HVS2/OH/ATT/D-Loop/7S DNA 1.41 1 1 1.070389 A189C
189 A G HVS2/OH/ATT/D-Loop/7S DNA 5.51 1 1 1.070389 A189G
379 A G OH/mt4H/ATT/D-Loop 0.01 1 0 Inf A379G
961 T C 12S 0.99 2 2 1.070389 T961C
961 T G 12S 0.38 2 2 1.070389 T961G
1187 T C 12S 0.08 1 0 Inf T1187C
1822 T C 16S 0.57 1 0 Inf T1822C
1842 A G 16S 0.33 1 0 Inf A1842G
1926 A G 16S 0.03 1 0 Inf A1926G
3333 C T ND1 0.14 1 0 Inf C3333T
3579 A G ND1 0.05 1 0 Inf A3579G
3666 G A ND1 2.77 1 0 Inf G3666A
5102 A G ND2 0.01 1 0 Inf A5102G
5252 G A ND2 0.34 1 0 Inf G5252A
6253 T C COI 1.11 1 0 Inf T6253C
6365 T C COI 0.32 1 1 1.070389 T6365C
6629 A G COI 0.27 1 0 Inf A6629G
6776 T C COI 1.94 2 2 1.070389 T6776C
7220 T C COI 0.07 1 0 Inf T7220C
8448 T C ATPase8 0.43 2 1 2.070389 T8448C
8540 T C ATPase8/ATPase6 0.02 1 0 Inf T8540C
8745 A G ATPase6 0.02 1 0 Inf A8745G
9181 A G ATPase6 0.22 1 0 Inf A9181G
10364 G A ND3 0.07 1 0 Inf G10364A
10653 G A ND4L 0.05 1 0 Inf G10653A
11410 T C ND4 0.16 1 0 Inf T11410C
11914 G A ND4 11.02 1 0 Inf G11914A
13404 T C ND5 0.18 1 0 Inf T13404C
13708 G A ND5 6.82 1 0 Inf G13708A
13759 G A ND5 2.93 2 1 2.070389 G13759A
14070 A G ND5 0.34 1 0 Inf A14070G
14587 A G ND6 0.53 1 0 Inf A14587G
14953 C T Cytb 0.12 1 0 Inf C14953T
16092 T C ATT/D-Loop/HVS1 1.47 1 0 Inf T16092C
16140 T C ATT/D-Loop/HVS1/7S DNA 1.30 1 0 Inf T16140C
16162 A G ATT/D-Loop/HVS1/7S DNA/TAS 1.43 1 1 1.070389 A16162G
16184 C T ATT/D-Loop/HVS1/7S DNA 0.72 1 0 Inf C16184T
16209 T C ATT/D-Loop/HVS1/7S DNA 2.72 1 1 1.070389 T16209C
16239 C G ATT/D-Loop/HVS1/7S DNA 0.06 2 0 Inf C16239G
16239 C T ATT/D-Loop/HVS1/7S DNA 1.06 2 0 Inf C16239T
16254 A G ATT/D-Loop/HVS1/7S DNA 0.13 1 0 Inf A16254G
16256 C T ATT/D-Loop/HVS1/7S DNA 3.60 1 0 Inf C16256T
16293 A G ATT/D-Loop/HVS1/7S DNA 2.28 3 1 2.655352 A16293G
16311 T C ATT/D-Loop/HVS1/7S DNA 20.66 3 1 2.655352 T16311C

Enriched in low LVSD (<-1fc)

tpos tnt qnt calc_locus gb_perc hot cold enrichment allele
150 C T HVS2/OH/ATT/D-Loop/7S DNA 11.81 0 1 -Inf C150T
152 T C HVS2/OH/ATT/D-Loop/7S DNA 25.84 1 6 -1.514573 T152C
204 T C HVS2/OH/ATT/D-Loop 6.07 0 1 -Inf T204C
242 C T HVS2/OH/TFX/ATT/D-Loop 0.39 0 1 -Inf C242T
249 A G HVS2/OH/TFX/ATT/D-Loop 0.17 0 1 -Inf A249G
249 A T HVS2/OH/TFX/ATT/D-Loop 0.00 0 1 -Inf A249T
408 T A OH/PL/ATT/D-Loop 0.21 0 1 -Inf T408A
575 C T D-Loop 0.11 0 1 -Inf C575T
951 G A 12S 0.79 0 1 -Inf G951A
1503 G A 12S 0.28 0 1 -Inf G1503A
1719 G A 16S 5.07 0 1 -Inf G1719A
2352 T C 16S 2.62 0 1 -Inf T2352C
2581 A G 16S 0.29 0 1 -Inf A2581G
2882 T C 16S 0.01 0 1 -Inf T2882C
3197 T C 16S 4.21 0 1 -Inf T3197C
3397 A G ND1 0.30 0 1 -Inf A3397G
3906 T C ND1 0.03 0 1 -Inf T3906C
4227 A G ND1 0.10 0 1 -Inf A4227G
4336 T C Q 1.04 0 2 -Inf T4336C
4512 G A ND2 0.06 0 1 -Inf G4512A
4736 T C ND2 0.17 0 1 -Inf T4736C
4793 A G ND2 0.85 0 1 -Inf A4793G
5054 G C ND2 0.07 0 1 -Inf G5054C
5460 G A ND2 6.25 0 1 -Inf G5460A
5471 G A ND2 1.06 0 1 -Inf G5471A
5480 A G ND2 0.18 0 1 -Inf A5480G
6126 A G COI 0.01 0 1 -Inf A6126G
7471 C T S(UCN) 0.05 0 1 -Inf C7471T
7645 T C COII 0.28 0 1 -Inf T7645C
7930 A T COII 0.13 0 2 -Inf A7930T
8429 C T ATPase8 0.04 0 1 -Inf C8429T
8602 T C ATPase6 0.16 0 2 -Inf T8602C
9163 G A ATPase6 0.06 0 1 -Inf G9163A
9391 C T COIII 0.07 0 1 -Inf C9391T
9489 G A COIII 0.02 0 1 -Inf G9489A
9581 T C COIII 0.14 0 1 -Inf T9581C
10217 A G ND3 0.12 0 1 -Inf A10217G
10493 T C ND4L 0.27 0 1 -Inf T10493C
10771 A G ND4 0.14 0 2 -Inf A10771G
11101 A G ND4 0.14 0 1 -Inf A11101G
11719 G A ND4 75.36 0 1 -Inf G11719A
11864 T C ND4 0.17 0 1 -Inf T11864C
11969 G A ND4 1.51 0 1 -Inf G11969A
14097 C T ND5 0.07 0 1 -Inf C14097T
14178 T C ND6 2.77 0 1 -Inf T14178C
14212 T C ND6 1.86 0 2 -Inf T14212C
14325 T C ND6 0.10 0 1 -Inf T14325C
14359 C T ND6 0.00 0 1 -Inf C14359T
14401 A G ND6 0.02 0 1 -Inf A14401G
14497 A G ND6 0.05 0 1 -Inf A14497G
14857 T C Cytb 0.06 0 1 -Inf T14857C
14861 G A Cytb 0.27 0 1 -Inf G14861A
14871 T C Cytb 0.02 0 1 -Inf T14871C
15430 C T Cytb 0.01 0 1 -Inf C15430T
15511 T C Cytb 0.30 0 1 -Inf T15511C
15646 C T Cytb 0.06 0 1 -Inf C15646T
15817 A G Cytb 0.11 0 1 -Inf A15817G
15833 C T Cytb 0.66 0 1 -Inf C15833T
15992 A G P/ATT 0.01 0 1 -Inf A15992G
16093 T C ATT/D-Loop/HVS1 5.66 0 2 -Inf T16093C
16126 T C ATT/D-Loop/HVS1/7S DNA 11.58 0 1 -Inf T16126C
16129 G A ATT/D-Loop/HVS1/7S DNA 13.07 0 2 -Inf G16129A
16129 G C ATT/D-Loop/HVS1/7S DNA 0.69 0 2 -Inf G16129C
16176 C G ATT/D-Loop/HVS1/7S DNA 0.21 0 1 -Inf C16176G
16176 C T ATT/D-Loop/HVS1/7S DNA 0.71 0 1 -Inf C16176T
16215 A G ATT/D-Loop/HVS1/7S DNA 0.25 0 1 -Inf A16215G
16220 A C ATT/D-Loop/HVS1/7S DNA 0.33 0 2 -Inf A16220C
16220 A G ATT/D-Loop/HVS1/7S DNA 0.06 0 2 -Inf A16220G
16261 C T ATT/D-Loop/HVS1/7S DNA 7.47 0 1 -Inf C16261T
16316 A G ATT/D-Loop/HVS1/7S DNA 0.88 0 1 -Inf A16316G
16316 A T ATT/D-Loop/HVS1/7S DNA 0.00 0 1 -Inf A16316T
16357 T C ATT/D-Loop/HVS1/7S DNA 1.09 0 1 -Inf T16357C
16390 G A ATT/D-Loop/7S DNA 5.82 0 1 -Inf G16390A

Sex differences in H

H has differences in the number of high LVSD subjects by gender. There is no discernable interaction with any H subclades.

## # A tibble: 4 x 3
##   sex   `lvsd >= 3`   cnt
##   <fct> <lgl>       <int>
## 1 1     FALSE          24
## 2 1     TRUE            2
## 3 2     FALSE          22
## 4 2     TRUE            8

T

Enrichment

Are there any differences in variants between the 3 >=3’s and the 7 0’s?

Enriched in high LVSD (>1fc)

tpos tnt qnt calc_locus gb_perc hot cold enrichment allele
152 T C HVS2/OH/ATT/D-Loop/7S DNA 25.84 3 2 1.807355 T152C
195 T C HVS2/OH/ATT/D-Loop 20.51 2 2 1.222392 T195C
239 T C HVS2/OH/TFX/ATT/D-Loop 1.31 1 0 Inf T239C
469 C T ATT/D-Loop 0.04 1 0 Inf C469T
5985 G A COI 0.11 1 0 Inf G5985A
9899 T C COIII 1.06 3 0 Inf T9899C
12633 C A ND5 1.21 3 0 Inf C12633A
12633 C T ND5 0.28 3 0 Inf C12633T
16163 A G ATT/D-Loop/HVS1/7S DNA/TAS 1.40 3 0 Inf A16163G
16186 C T ATT/D-Loop/HVS1/7S DNA 1.24 1 0 Inf C16186T
16189 T C ATT/D-Loop/HVS1/7S DNA 25.41 1 0 Inf T16189C
16311 T C ATT/D-Loop/HVS1/7S DNA 20.66 1 1 1.222392 T16311C

Enriched in low LVSD (<-1fc)

tpos tnt qnt calc_locus gb_perc hot cold enrichment allele
194 C T HVS2/OH/ATT/D-Loop 1.73 0 1 -Inf C194T
207 G A HVS2/OH/ATT/D-Loop 4.69 0 1 -Inf G207A
321 T C HVS2/OH/HPR/ATT/D-Loop 0.04 0 1 -Inf T321C
930 G A 12S 2.04 0 4 -Inf G930A
3204 C T 16S 0.37 0 1 -Inf C3204T
3398 T C ND1 0.36 0 1 -Inf T3398C
5147 G A ND2 4.12 0 4 -Inf G5147A
5277 T C ND2 0.26 0 1 -Inf T5277C
5426 T C ND2 1.05 0 2 -Inf T5426C
5460 G A ND2 6.25 0 1 -Inf G5460A
5747 A G OL 0.09 0 1 -Inf A5747G
6489 C A COI 0.21 0 1 -Inf C6489A
7295 A G COI 0.02 0 1 -Inf A7295G
8537 A G ATPase8/ATPase6 0.07 0 1 -Inf A8537G
8572 G A ATPase8/ATPase6 0.28 0 1 -Inf G8572A
8854 G A ATPase6 0.08 0 1 -Inf G8854A
9233 T C COIII 0.13 0 1 -Inf T9233C
11242 C G ND4 0.06 0 1 -Inf C11242G
11812 A G ND4 3.30 0 7 -Inf A11812G
12373 A G ND5 0.15 0 1 -Inf A12373G
13260 T C ND5 0.21 0 1 -Inf T13260C
13708 G A ND5 6.82 0 1 -Inf G13708A
14233 A G ND6 3.66 0 7 -Inf A14233G
15028 C A Cytb 0.20 0 1 -Inf C15028A
15043 G A Cytb 22.77 0 1 -Inf G15043A
16224 T C ATT/D-Loop/HVS1/7S DNA 5.00 0 1 -Inf T16224C
16278 C T ATT/D-Loop/HVS1/7S DNA 10.27 0 1 -Inf C16278T
16296 C T ATT/D-Loop/HVS1/7S DNA 2.25 0 1 -Inf C16296T
16304 T C ATT/D-Loop/HVS1/7S DNA 6.57 0 1 -Inf T16304C

T1 vs T2

T1 and T2, appear to segregate strongly with regard to LVSD.

The major subclades of T are distinguished by just a few loci.

T1 is defined by C12633A A16163G T16189C

T2 is defined by A11812G A14233G (C16296T)

See http://www.ncbi.nlm.nih.gov/pubmed/19434233

T subclade summary

twoletterhaplogroup cnt mean range sd
T1 7 2.3571429 1-4 1.0293317
T2 9 0.2777778 0-1.5 0.5651942

Logistic regression assuming lvsd>1 is affected

## 
## Call:
## glm(formula = affected ~ twoletterhaplogroup, family = binomial(link = "logit"), 
##     data = Tdf)
## 
## Deviance Residuals: 
##     Min       1Q   Median       3Q      Max  
## -1.9728  -0.4854  -0.4854   0.5553   2.0963  
## 
## Coefficients:
##                       Estimate Std. Error z value Pr(>|z|)  
## (Intercept)              1.792      1.080   1.659   0.0971 .
## twoletterhaplogroupT2   -3.871      1.514  -2.557   0.0105 *
## ---
## Signif. codes:  0 '***' 0.001 '**' 0.01 '*' 0.05 '.' 0.1 ' ' 1
## 
## (Dispersion parameter for binomial family taken to be 1)
## 
##     Null deviance: 21.930  on 15  degrees of freedom
## Residual deviance: 12.021  on 14  degrees of freedom
## AIC: 16.021
## 
## Number of Fisher Scoring iterations: 4

Logistic regression by the outcome variable (ignoring -9’s)

## 
## Call:
## glm(formula = status ~ twoletterhaplogroup, family = binomial(link = "logit"), 
##     data = Tdfo)
## 
## Deviance Residuals: 
##      Min        1Q    Median        3Q       Max  
## -0.51678  -0.51678  -0.25837   0.00005   2.03933  
## 
## Coefficients:
##                       Estimate Std. Error z value Pr(>|z|)
## (Intercept)              20.57    7238.39   0.003    0.998
## twoletterhaplogroupT2   -22.51    7238.39  -0.003    0.998
## 
## (Dispersion parameter for binomial family taken to be 1)
## 
##     Null deviance: 19.4081  on 13  degrees of freedom
## Residual deviance:  6.0283  on 12  degrees of freedom
## AIC: 10.028
## 
## Number of Fisher Scoring iterations: 19

Next steps

  • Parsable Phylotree
  • Build mixed model, test at different levels (macro, two-letter, three-letter)
  • Look at heteroplasmies
  • Investigate burden of variants - especially in ND4 and ND6
  • Develop RF or other ML approaches for classification